1. Field of the Art
This invention relates to highly hydrated polymers and more specifically to highly hydrated polymer surfaces grafted onto polymer substrates for use in medical devices.
2. Discussion of the Prior Art
There is evidence that highly hydrated polymers may be biocompatible and resistant to formation of blood clots and thromboemboli. However, hydrophilic polymers generally have low physical strength in aqueous environments so that useful, long-lived prosthetic devices and medical instruments cannot be produced from them. To overcome this drawback, techniques have been developed for grafting monomers such as n-vinyl-2-pyrrolidone, 2-hydroxyethyl methacrylate, and others, onto polymer substrates (e.g. silicone rubber, polyurethane, polyesters, polyolefins, polyvinylchloride, copolymers, etc.) These techniques produce a composite material having a hydrophilic surface on a strong, stable backing useful for prosthetic devices such as heart valves, poppets, implantable catheters, intrauterine devices, mammary prostheses, neuroshunts, medical tubings used in heart bypass operations and kidney dialysis procedures for the extracorporeal circulation of blood and power pack coverings for heart assist devices.
One such grafting procedure as taught in U.S. Pat. No. 3,939,049 to Ratner, et al. utilizes a mutual irradiation technique. A polymer substrate is fully immersed in a mixture of monomer and solvent and placed adjacent to a source of gamma radiation. After irradiation, the grafted polymer specimen is removed from the surrounding medium and cleaned. The surrounding medium, at this point, generally consists of polymer, unreacted monomer, and solvent and can be fully liquid, a tough crosslinked gel, or a combination of the two, depending upon reaction conditions. When the surrounding medium, the polymerization "solution," forms a crosslinked gel, homopolymerization of the monomer is occurring.
To obtain an evenly grafted surface film, it is usually desired that the surrounding medium be fully liquid, that is, that homopolymerization be inhibited. According to Ratner, et al., in the case of silicone rubber and a polyurethane-polyether copolymer, gelation of the homopolymer surrounding the grafted film can be inhibited by the presence of cupric salts. For polyethylene, however, the degree of graft is highest in the absence of the cupric salt. In the case of n-vinyl-2-pyrrolidone grafted onto silicone rubber, presence of the salt increases the amount of material grafted; however, increased penetration of the graft into the silicone rubber is associated with increased concentration of cupric ion. Thus, the salt needed to accomplish surface-grafting differs with the chemical properties of the polymeric substrate and the surface monomer.
There are two drawbacks in the Ratner process for application to the manufacture of medical devices. First, with a silicone matrix, the graft tends to become incorporated within the silicone matrix rather than remaining on the surface, thus defeating the purpose of the grafting procedure. Second, the mutual irradiation technique is expensive and requires specialized equipment to administer.
U.S. Pat. Nos. 4,311,573 and 4,589,964 to Mayhan et al. describe procedures for producing a graft copolymer utilizing many substrates, including silicone, and ethylenically unsaturated compounds such as methacrylamide, sodium methacrylate, or others, as the monomer wherein the substrate is peroxidized to produce a radical for bonding the graft. Polymerization takes place in the presence of iron salts, specifically ferrous ammonium sulfate, as a graft polymerization initiator and homopolymerization inhibitor. Polymerization can be initiated in the presence of squaric acid, which reduces the metal ions from their oxidized state after they have initiated a grafting reaction under acidic conditions. However, n-vinyl pyrrolidone is hydrolyzed in an acidic aqueous environment.
U.S. Pat. No. 3,627,836 to Getson discloses a method of grafting monofunctional and polyfunctional olefinic monomers to organopolysiloxanes. The monofunctional monomers include n-vinyl pyrrolidone and the polyfunctional monomers include esters of acrylic and methacrylic acid. However, in this process homopolymerization occurs to some extent. Due to homopolymerization the amount of the surface graft is not sufficient to form the lubricious, hydrophilic surfaces.
U.S. Pat. No. 3,631,087 to Lewis, et al. describes another conventional process for grafting organopolysiloxanes by the gradual addition of unsaturated monomers in the presence of free-radical initiators, i.e., peroxides. Generally, the preferred range of monomer addition is from about 0.5 to about 200 parts per 100 parts of polysiloxane. Although acrylic acid esters and n-vinyl pyrrolidone are disclosed as suitable monomers, there is no indication that they can be used in combination with unexpectedly good results.
U.S. Pat. No. 4,729,914 to Kliment et al. discloses a method of grafting hydrophilic polyvinylpyrrolidone coatings by applying to a substrate having active hydrogen sites a copolymer of vinylpyrrolidone containing free isocyanate groups capable of reacting with the substrate. Chemical bonds between the isocyanate and the active hydrogen sites prevent leaching of polyvinyl-pyrrolidone from the substrate during use. However, this method of grafting requires that the substrate contain active hydrogen sites on the surface.
As can be seen from the foregoing, the need exists for new and better methods for modifying the surface characteristics of polymeric substrates with n-vinyl pyrrolidone to provide the lubriciousness and hydrophilicity that renders such graft polymers useful in medical and other applications.